AB0581 CLINICAL AND RENAL PATHOLOGICAL FEATURES PREDICTING COMPLETE CLINICAL RESPONSE IN CRESCENTIC LUPUS NEPHRITIS
Authors: H. Fukui, H. Hanaoka, K. Saito, K. Hiramoto, S. Saito, J. Kikuchi, Y. Kaneko
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Lupus nephritis (LN) is one of the major manifestations of systemic lupus erythematosus, which develops in approximately 40% of patients with systemic lupus erythematosus. Clinical presentation of LN varies between patients, from asymptomatic proteinuria to rapidly progressive glomerulonephritis. Due to improvements in treatment strategy, risk of developing end-stage kidney disease (ESKD) decreased to less than 10% in developed countries, but some patients still progress to ESKD and require renal replacement therapy. Crescent formation is considered as a poor prognostic factor in LN, however pathological features correlating with clinical response and long-term renal outcome has not been fully investigated. <h3>Objectives</h3> To determine clinical and pathological features predicting complete clinical response (CCR) after induction therapy in crescentic lupus nephritis (CLN) comparing with non-CLN. <h3>Methods</h3> Patients with biopsy proven class III or IV LN from 2008 to 2017 and who could be observed more than 5-years after induction therapy were selected. They were divided into two groups according to the presence of cellular crescentic lesions. Individual pathological lesions defined in modified NIH activity and chronicity indices were evaluated. CCR was defined as urinary protein-to-creatinine ratio (UPCR) less than 0.7g/day after 12 months of treatment, according to the 2019 EULAR/ERA-EDTA recommendations for LN. Cumulative CCR rates for 5-years were compared between the two groups, and independent factors associated with CCR were investigated. <h3>Results</h3> Seventy-three patients (CLN, 30 patients and non-CLN, 43 patients) were included in the analysis. There was no significant difference in age (42.8 ± 2.6 vs 44.4 ± 2.1 years, p=0.63), disease duration (10.9 ± 1.9 vs 11.4 ± 1.7 years, p=0.85), eGFR (70.7 ± 4.9 vs 66.0 ± 4.1 ml/min/1.73m<sup>2</sup>, p=0.47), and UPCR (2.3 ± 0.5 vs 2.5 ± 0.4 g/gCr, p=0.72) between the CLN and non-CL groups. Cumulative CCR rates for 5-years were not different between CLN and non-CLN groups (83% vs 84%, p=0.96). In the non-CLN group, patients who achieved CCR had lower glomerular sclerosis (0.93 ± 0.16 vs 1.75 ± 0.27, p=0.01) and interstitial fibrosis score (0.77 ± 0.12 vs 1.25 ± 0.20, p=0.049) than those who did not achieve CCR. In the CLN group, patients who achieved CCR had lower interstitial fibrosis (0.94 ± 0.14 vs 1.67 ± 0.17, p&lt;0.01) and tubular atrophy score (0.78 ± 0.15 vs 1.58 ± 0.19, p&lt;0.01) than those who achieved CCR, while cellular or fibrotic crescentic score did not differ between them (2.33 ± 0.23 vs 2.50 ± 0.23, p=0.65). Multivariable analysis revealed that interstitial fibrosis was negatively associated with CCR in both CLN and non-CLN groups (odds ratio [OR] 0.11, p&lt;0.01; OR 0.33, p=0.04, respectively). We next divided CLN patients into two groups according to the interstitial fibrosis less than 25% or not, and found significantly higher cumulative CCR rate in patients with interstitial fibrosis less than 25% (p&lt;0.01). <h3>Conclusion</h3> Crescent formation in the kidney pathology was not associated with cumulative CCR rates in patients with class III or IV LN, while interstitial lesion was shared by both CLN and non-CLN as a significant prognostic factor for CCR after induction therapy. <h3>References</h3> [1]Yu F, Tan Y, Liu G, Wang SX, Zou WZ, Zhao MH. Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. <i>Kidney Int</i>. 2009;76(3):307-317. [2]Bajema IM, Wilhelmus S, Alpers CE, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. <i>Kidney Int</i>. 2018;93(4):789-796. [3]Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. <i>Ann Rheum Dis</i>. 2020;79(6):713-723. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.